Sarepta Therapeutics, Inc. (SRPT) Earnings Call Transcript & Summary

Good day, and thank you for standing by. Welcome to the Sarepta Therapeutics SRP-9001 BLA update conference call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Doug Ingram, President and Chief Executive Officer. Please go ahead, sir.

Thank you, Norma. Good evening, and thank you for joining our update call regarding the Biologics License Application, or BLA, for SRP-9001, our investigational gene therapy to treat Duchenne muscular dystrophy. As you will have seen in our accompanying release, we completed our late-cycle review this week and the FDA's Office of Therapeutic Products, or OTP, has now determined that they will hold an advisory committee, or Adcom, meeting for the SRP-9001 BLA. As Duchenne muscular dystrophy is a devastating and life-ending disease and time is of the essence for the thousands of families living with Duchenne, the Center for Biologics Evaluation and Research, or CBER, has informed us that they are working to schedule the advisory committee meeting expeditiously and prior to the May 29, 2023, action date. It is our understanding that the date for the Adcom will be posted by the FDA within the next week. And once posted, we will issue a press release in that day. The decision on the Adcom represents a change in OTP's position from the midcycle review. As we reported on our earnings call 2 weeks ago, at the midcycle review, OTAT, the predecessor to OTP, informed us that they did not intend to hold an advisory committee for SRP-9001. And when asked at the midcycle meeting confirmed that they saw no circumstances in which this decision would change. The division also provided final minutes of the midcycle meeting on February 23, 2023, three business days before our earnings call, confirming that no advisory committee was forthcoming. Additionally, the day before our earnings call, we sought and obtained confirmation from FDA that no advisory committee was planned. It is our understanding that this change in decision results from the following: OTAT has been reorganized, and the super office OTP has been established. As Dr. Peter Marks, the Director of CBER, has publicly confirmed CBER and OTP intend where appropriate, to explore the innovative use of surrogate endpoints, biomarkers and the accelerated approval pathway to advanced cell and gene therapies, in particular, for rare life-ending degenerative diseases. As the 9001 application is one of the first gene therapy BLA's founded on a surrogate endpoint, CBER and OTP believe it appropriate to take expert advice in a public forum. It is our understanding that as safety is not identified as a significant issue, the primary topic of the advisory committee will be the design of the 9001 construct and the evidence supporting the conclusion that 9001 dystrophin is reasonably likely to predict clinical benefit, which is, of course, the standard for accelerated approval. I am, of course, disappointed to announce a change in the division's decision about an advisory committee so soon after we informed you that OTAT did not intend to hold an advisory committee. But my disappointment is limited to the timing of these decisions, not with the substantive decision to hold an advisory committee. It had always been our expectation that an advisory committee would be part of the review, and we see it as an opportunity to publicly share the robust evidence supporting the benefits of SRP-9001 in a public forum. Please be assured that we have been planning and preparing for an advisory committee from the moment we submitted this BLA in the fall of 2022. And as such, we will be well prepared for this outcome, and we look forward to presenting the wealth of evidence supporting the transformative potential of SRP-9001. We also believe that the BLA review will be well informed from hearing the perspectives of Duchenne experts, clinicians, clinical investigators and the patient community on the importance of SRP-9001 and the evidence of its benefits to the lives of patients who every day are being irreparably harmed by this ferocious degenerative disease. As I am providing an update on the BLA review, OTP, again in the late-cycle meeting did not identify any significant safety issues with SRP-9001 and indeed informed us that they do not anticipate the need for a risk management program for SRP-9001. I will also say that we have by now completed the 2 manufacturing inspections at the Catalent facilities. Both reviews concluded successfully, one with no observations and the other with only 2 observations, neither of which will impact product approval. The third and final inspection of the Sarepta site will be conducted soon. And with that, I will open the call to questions. Norma?

[Operator Instructions] Our first question comes from the line of Brian Abrahams with RBC.

I was wondering if I could drill down maybe a little bit more on why the change here, whether this stems from just the evolution in FDA's thinking in the field overall, the changes in leadership at OTP or any new data emerging from you or other gene therapies in the field? And then I guess I'm also curious your level of confidence that you won't need a major amendment in order to accommodate the time lines here?

Thank you for the question, Brian. So what I can say is that there was no new information provided. So this doesn't appear to be related to any new evidence. I think broadly speaking, it relates to the change in the decision of the division that they'd like to have an advisory committee to explore the surrogate endpoint, particularly, I suspect on as the OTP and the leader of CBER, Dr. Marks, has repeatedly publicly noted that he would like to start looking where appropriate at innovative approaches like surrogate endpoints and accelerated approval. As it relates to a major amendment, we have no basis to believe that as we sit here today. In fact, I think that we're very encouraged by the fact that, while this decision on an Adcom came later than one would have expected, nevertheless, the division and CBER are working very hard to ensure that this does not affect the delay in our action date and intend to schedule this advisory committee within the time before the May 29 action date. So as we sit here right now, we're very encouraged by that, and we don't see any basis today for a major amendment.

Our next question comes from the line of Brian Skorney with R.W. Baird.

I guess also if we're going to get a lot of good questions in different forms, but I mean, was there anything brought up in the late cycle review meeting in terms of sort of the surrogate and the strength of evidence that you have around the surrogate of SRP-9001-produced dystrophin that was a change from the midcycle review meeting? And do you know -- have they said if this is going to be a virtual outcome? Any chance of a live outcome?

Yes, so I'll answer the last question. We don't know the answer on live versus virtual, although it's my understanding most recently that the bulk of advisory committees have been virtual. I think that the big change between the late cycle and the midcycle was that there was discussion of surrogacy of 9001 and the discussion of the evidence to support the conclusion that 9001 is reasonably likely to predict clinical benefit, which presumably is the primary topic at the advisory committee that will occur before the action date.

Our next question comes from the line of Colin Bristow with UBS.

Thanks for hosting this and the transparency. So has FDA requested any additional clinical data? And from EMBARK, I know you provided to 120-day safety data. I'm just curious, anything additional from EMBARK expected to be provided prior to the PDUFA? And then on the site that remains expected, I believe this is the release assay site. Can you just give any color around sort of prior inspections or preparedness that could give us some comfort into this remaining inspection?

Yes, so on the first question about additional data, there will be the best of my -- I believe no additional data provided in advance of the Adcom. We've already provided all of the analysis and data that supports -- from our perspective, the very robust support for the conclusion that 9001 is reasonably likely to predict clinical benefit and comfortably exceeds that bar. As it relates to the inspection, so the most significant of the 3 inspections were the Catalent inspections, both of those have successfully concluded. To the best of my knowledge, we haven't had an independent inspection of our Andover site, but that will be occurring very soon. I think the team is well prepared to have a successful site inspection there. And that is for a couple of the assays related to the release of the product. So we're in good shape there as we stand here today, and we're in great shape from inspections generally.

Our next question comes from the line of Tazeen Ahmad with Bank of America.

Just on how FDA plans on handling the date of the Adcom. So is it still possible that, depending on when the Adcom is held, the FDA can then potentially institute a 3-month extension on the PDUFA just because, I don't know, maybe it takes them a certain amount of time to get this committee together. And if they feel it happens some time in April or something, it's not going to allow them enough time to get back to you in May. Did they indicate to you whether a PDUFA push was on the table at this stage?

There has been no indication today that there is any push or change or new PDUFA date. And in fact, I and the team are very encouraged by the fact that, notwithstanding, that this is a relatively late decision on an advisory committee. I think the agency is going above and beyond to ensure that they're very mindful of the PDUFA date, May 29, and they're going to schedule this meeting in advance of that PDUFA date, which gives me some confidence that they understand the importance to the patient community of hitting our time lines.

Our next question comes from the line of Salveen Richter with Goldman Sachs.

This is Tommie on for Salveen. Just curious if you're aware of any precedent for the agency communicating that there will be no Adcom and then changing your mind afterward, or if you think that this is more so specific to the current situation with OTAT reorganizing into OTP. And in your discussions in late-cycle review, just I'm wondering about, has there been any feedback on the trial design or any of the functional data that you've collected here?

Yes. So I think there are certainly historical instances of this division and others having changes of view on hosting Adcom. I think it's occurred relatively recently actually in the last -- certainly, in the last 12 months, I believe, with other programs. And notwithstanding the fact that the agency had fairly firmly informed us that there wouldn't be an Adcom as of the midcycle. It's within the prerogative of the division to change its view and to have an Adcom. As I have said earlier, disappointed certainly that we have had to inform you of a change in position. It would have been, of course, much easier to have told you this a few weeks ago in connection with our earnings call, but we're not disappointed with the advisory committee itself. We actually do see this as a real opportunity to share the information. And then on the late cycle, I'm not going to go into a ton of detail on the review while it's active other than to say that there will be a discussion at the advisory committee about the data that supports 9001 and the use of 9001 dystrophin, which is a functional shortened version of dystrophin as reasonably likely to predict clinical benefit. So I think we're going to be -- we're going to present very well at that advisory committee, and I look forward to it.

Our next question comes from the line of Hartaj Singh with Oppenheimer.

Doug, just a quick question, building on the last response that you just gave. You presented a lot of data on long-term clinical data [indiscernible]. You've also had data for various studies. I believe you presented data at WMS last year on showing how dystrophin and clinical functionality are actually correlated. Can you just go over that a little bit? Talk about the data you've already collected and the data that should be going into that review package to the FDA for the Adcom.

Well, there is -- I can go very broadly that there's a wealth of data that has been collected on the use of 9001 as reasonably likely to predict clinical benefit. It starts -- I'll give you the most broad strokes. That issue and the standard require one to look at the totality of evidence, and the totality of evidence is, in my opinion, very robust, far exceeding, we think, the standard and certainly as good as or, frankly, much better than the precedents that exist, and there are 4 precedents already of using shortened functional dystrophin as reasonably likely to predict clinical benefit successfully so. That starts with the design of this construct. This construct was designed, informed by epidemiology and natural history, designed over a decade to ensure that the regions in this dystrophin that conferred functional benefit were preserved. Then it was tested in animal models, looking at both function and biomarkers, confirming that Dr. Louise Rodino-Klapac and her colleague, Dr. Jerry Mendell, were successful in achieving those results. And then, of course, we have -- which is pretty rare in -- for accelerated approval. And then we go to clinical data and human data, we have a wealth across multiple studies and longitudinally across multiple studies, data that shows the impact expression level and effect on biomarkers of 9001. And then finally, we even have significant amounts of clinical data indicating the benefits of 9001, something that is somewhat rare for an accelerated approval. We also have very robust expression across multiple studies. And as I've mentioned before, and I think acknowledged by the agency, we not only get great expression, but we have a very laudable safety profile as well. So all of that will come into the discussion at an advisory committee. I think that primary discussion topic will be accelerated approval in the use of 9001 dystrophin as a surrogate endpoint reasonably likely to predict the clinical benefit.

Our next question comes from the line of Matthew Harrison with Morgan Stanley.

I guess, Doug, I was just hoping you could take a moment to clarify some things that you said. So I think you said part of the change may be related to -- from the midcycle to the late cycle review is around the sort of questions that you got or the view that you have on use of the surrogate endpoint. I was just hoping you could clarify exactly what you meant and if there was a change in terms of how the FDA was communicating? And then separately, would you just be willing -- I don't know if there's been any comment from the FDA around the composition for the panel or what to expect in terms of composition?

The second question I can answer immediately. No, there has been no discussions over the composition of the panel. So we'll wait and see that. What I can really say about the change, does it relate to additional or new data or additional or new analyses. The most -- there are a couple things to know, of course. There is a transition between OTAT to the super-office OTP, and presumably, that may relate in some way to some of the decisions or at least evaluations of decisions. I think the fact that we are using accelerated approval pathway and using the concept of 9001 as a surrogate endpoint is the topic that is likely to be the primary discussion topic at the advisory committee. I think the fact that this is one of the first times that this accelerated approval pathway and surrogate endpoints are being used for an in vivo gene therapy plays some role in this decision. And then some part of it just relates to the fact that the division does have the right to change its mind on things. And I think that happened here. And the good news on this is that, number one, that we had always assumed that we were going to have an advisory committee. It was only very recently in the last couple of weeks did we envision that we weren't going to have an advisory committee. So we will be very well prepared to present well and show up well at this advisory committee. We're looking forward to that. And number two, we have, from our perspective, a very robust set of evidence that supports the conclusion that 9001 dystrophin is reasonably likely to predict clinical benefit. In fact, of the issues that one would want to discuss, that's probably one of the ones we're most excited to discuss publicly.

Our next question comes from the line of Judah Frommer with Credit Suisse.

Just curious, did you get any indication of how the panel might look at clinical versus commercial-grade material? And can you just remind us, in terms of kind of durability of effect, I think you do have functional data out to multiple years. But for how many patients do you have dystrophin...

Yes, I missed the last part of that question, I apologize, Judah. So to answer that -- I'm sorry, go ahead.

No, I was just going to say how many patients do you have dystrophin expression data out for a length of time that sort of matches functional data?

We have a significant number of patients over multiple studies, a subset of which goes out to 4 years and 3 years and 2 years. As it stands right now, durability hasn't been a topic of significant issue for us. And how the Adcom itself will look at, for instance, like a nuance like the commercial material versus the clinical material, well, we don't even know the makeup of the Adcom yet. So we'll know that when we go have that discussion. But let's be clear, the standard is reasonably likely to predict clinical benefit that there is -- some of the material was made using an adherent process on HYPERstack, and some of the studies was based on adherence in iCELLis, but the end result was the same exact construct. So at least from an evidentiary perspective, one would assume that they are of equal interest in evaluating the question at hand, which would be to what extent is this 9001 dystrophin thoughtfully designed over a decade and tested before it went into patients and then went into significant patients. To what extent is it reasonably likely to predict clinical benefit? I would suggest that so long as the expression is similar, and it is, so long as the safety is similar and it is that the evidentiary value of both of those, at least from our perspective, ought to be the same and -- but of course, that we'll leave that to the advisory committee to see if they agree with our perspective.

Our next question comes from the line of Kristen Kluska with Cantor.

This is Rick on for Kristen. You laid out pretty clearly the topic of discussion at the Adcom will revolve around the -- likely revolve around the surrogate endpoint, and it's reasonably likely to predict clinical benefit and that this is a focus for the agency in rare daily indications. Are you in the team looking at any previous Adcoms that the agencies conducted that touched on surrogate endpoints in this way for an understanding of how the agency might look at this Adcom?

I'm sure the team is going to do diligence on those sorts of issues as well, as well as doing diligence to understand the makeup of the particular advisory committee once we know what it is. I would suggest that the team is also already very well versed in the standard for accelerated approval and the surrogacy of the 9001 dystrophin, and we're already very far along in preparing ourselves for that advisory committee. We've already, as an example, had mock -- we've had mock Adcoms. We're in a good place to understand the data and the evidence, of course, and I think we'll be very well prepared to discuss these issues with the advisory committee.

And the next question comes from the line of Zhiqiang Shu with Berenberg.

Doug, you mentioned the team is excited to present -- to discuss the data with the committee. I wonder, can you comment on how much of educational purpose of this Adcom would be to the broader community? And related to that, I guess, do you expect to see a voting question at the end? What do you expect just -- what that could be?

Yes. I really apologize. I think you broke up. I missed the first part of the question.

Sure. So I wonder if you can talk about how much of educational value for this Adcom could be to the broader community?

Well, I think it will. It's a very interesting question. I mean, I think one of the -- look, as long as we're going to have an Adcom, we're excited about this topic as we have an opportunity to share this data in a public forum, not only with the advisory committees, but with the rest of the public clinicians, physicians, investigators, the patient community and the like. And I think that will be very helpful to us. And I think in the end, it probably -- if we're fortunate enough to get approval, it'll probably be helpful even beyond that as we seek to get access and reimbursement for these kids. So I think there's a real value there. There will be voting questions at the end. I don't presume to know exactly what they are. The advisory committee will come up with the questions that will guide the discussion and then the voting, but presumably, one of those questions, I think you would envision, if not the primary question, is, based on the totality of evidence both preclinical and clinical biomarker and others and the design and natural history and the like is the 9001 dystrophin protein expressed in the amounts that we see in the patients here easily likely to predict clinical benefit. And there may be other questions as well. There may be questions about safety, although I must say that both in the midcycle and in the late cycle, the agency has not identified any significant safety issue. So I do think that the primary dominant question for the advisory committee is simply to review the wealth of evidence on 9001 and determine if, in their view, it's reasonably likely to predict the clinical benefit.

Our next question comes from Anvita Gupta with Cowen.

Doug, 2 questions for you. The first 1 is does the FDA have access to raw EMBARK data such that they could do an interim analysis?

No.

Okay.

More than they ask for. Other than safety data, they have all the safety data.

Got it. The second question is, was there any published data not by your team that could impact the review, particularly wondering if there was anything new published by others in the field on the construct or other DMD mutation analysis that could -- that was done and that would probably cut new doubt on the microdystrophin function?

So to the best of my knowledge, the answer to that's no, not at all. I'm very confident that the decision doesn't relate to any new analysis or new data but just relates to a change in decision in the division to hold an Adcom on this issue.

Our next question comes from the line of Danielle Brill with Raymond James.

This is Alex on for Danielle. Just kind of interested if you had any color on the normal cadence of the types of analyses the FDA normally performs at this point in the review cycle, just given that the question is about the adequacy of the surrogate endpoint. Do you think there's -- this decision was triggered by any statistical review of patient-level data or potentially the suitability of the natural history comparison?

I think broadly speaking, I don't think it relates to any sort of late-breaking analytics. I think in the broadest of strokes, it relates to just a change in view from the division on the wisdom of taking extra outside expert advice on this issue. And while -- it came as a surprise to us that there was a change in position. One of the reasons that we had always said that we anticipated an advisory committee meeting, up to the midcycle and even thereafter, we confirmed it repeatedly that there wouldn't be one. The reason we thought there was going to be one was because it is not irrational or unreasonable when we're dealing with an accelerated approval and certainly one of the first accelerated approval and the use of a surrogate endpoint in connection with the gene therapy to have an advisory committee in to review this in a public forum. So I think it's just a reconsideration and change in view is the best information that we have on this.

Our next question comes from Anupam Rama with JPMorgan.

Doug, if I could dig in a little bit on the surrogate endpoint of reasonably predictive of clinical benefit, which you repeated a lot on this call. Are they comfortable with the external control analysis? I realize that, that was prespecified. But is that -- is the validity of that going to be called into question as a reasonable way of underscoring clinical benefit?

Yes. Well, I'll get to the Adcom and see what the focus is that the Adcom. Let's be very clear, the issue in trying to deconstruct this is that, to decide whether something is reasonably likely to predict clinical benefit, we have to look at the totality of evidence, which means we have to go back, not go to the end but start at the beginning. How did this construct get designed? Why did it get designed? What was the design template for it? What natural history existed that informed how one might design it? How was it tested? What constructs were abandoned? What constructs were kept? What regions were kept? Why were they kept? Then we look at the preclinical data. What was its impact on biomarkers? What was its impact on function? Then we go to patients. What's the expression look like? What's the safety look like? What's the impact on biomarkers here? We're talking about things like everything from reductions in CK, which is a very, very important biomarker, as well as upregulation of the dystrophin-associated protein complex, which at least in my humble opinion is extraordinarily powerful indicia of the benefits of 9001. We're literally reconstructing the rest of the dystrophin-associated protein complex in the presence of the 9001 protein, and then we're going to walk over and talk at the Adcom about the clinical results, which in this sense is really additional powerful evidence that you normally don't get for accelerated approval. And as it relates to that, I'm sure we'll -- the advisory committee is going to want to understand what did we do from a natural history perspective an external control perspective. And again, this is going to be one of the issues that we're very excited about talking about because the way we constructed the external control was just about as rigorous as you can get. I mean, it is a synthetic placebo arm, in essence. We use multiple factors, use this propensity analysis to ensure that we didn't get the right matching simply on means, but we actually got the same distribution. And so, what issues are going to come up with at the Adcom and what discussions are going to be had, and what challenges we're going to get, we'll have to wait to the Adcom to have, but we're excited to talk about all of those issues because we think that this program and the way it's been designed and the rigor with which it's been executed is going to present very well for 9001, which in the end is going to be an enormous benefit for the thousands of patients with Duchenne muscular dystrophy who deserve to have us fight for an innovative approach to bringing this therapy to them as fast as possible.

And our next question comes from Debjit Chattopadhyay with Guggenheim Partners.

This is Robert on for Debjit. Has the FDA indicated anything on the timing of labeling discussions? Or is that a post-Adcom meeting item? And also, is there a minimum threshold for NSAA benefit that has been discussed with the FDA?

On labeling, I think it's still early for labeling discussions. We've given them a proposed label, but those labeling discussions will occur. Even in the absence of an Adcom, I think we're a little early for labeling discussions. And no, on NSAA, there's not a threshold issue. On NSAA, again, I would point out that this is accelerated approval, so we have to really look at the totality of all of that evidence. One of the big pieces of that evidence but sort of late in the downstream on the discussion is the effect that we have natural NSAA, which for those who are listening, that is the North Star Ambulatory Assessment. It's one of the primary functionable endpoints that we've used in our various studies, and we've seen a very impressive impact on NSAA. You look at those kids just something to shout out for -- kids that are out 4 years. I mean, they're 4 years on a 34-point scale, they're 9.5 points or so better than natural history, and they're 7 points above their own baseline, and they're over 9 years old, and they should be in steep decline and they're not. So I think as an additional evidence of the surrogacy of the 9001 dystrophin protein, the NSAA is going to be powerful.

Our next question comes from the line of Joseph Schwartz with SVB Securities.

Great. I was wondering kind of a similar question to what we asked in your last call. To what extent do you think the FDA will want to explore a quantitative and/or qualitative assessment of the microdystrophin that SRP-9001 produces in Duchenne patients? And how much precedent do you think the EXONDYS approval can provide if these are questions that come up in the FDA's assessment during the panel?

I'm going to apologize, Joe. I don't fully understand the first part of your question. Can -- maybe state again or rephrase it just so I can...

Yes, I'm sorry. So yes, I guess just because -- it's my understanding that around 60% of the native wild-type dystrophin gene is not encoded for with the microdystrophin, including yours. And so I'm just wondering, do you think that the FDA will want to explore the significance of that and maybe even try to quantify it or qualify it to understand what the domains that are included do? And it's my understanding that we don't fully understand what every domain of dystrophin does even.

Okay. Great. Excellent. Excellent. Well, the short answer is, I hope so. I hope that's a big focus of the Adcom because they are the folks around here that understand the various domains and their value, there are a few that understand them as well as Dr. Louise Rodino-Klapac who, in addition to being currently our Head of R&D, spent a decade thoughtfully designing, testing, redesigning and testing the various constructs and domains to come up with 9001, which I will also note, does have a -- it does have an analogy in natural history. There are instances of heavily edited versions of dystrophin that remain perfectly functional so long as you have preserved the right domain. So we're really looking forward to the opportunity to have those discussions and really walk through with an advisory committee thoughtfully how this construct was designed and why certain regions were kept and other regions were less necessary and how that in addition to being functional and providing functional benefit, how that relates to some of the blueprint, the template that was used from natural history. There's the 61-year-old gentleman who was perfectly ambulatory and had a mutation that resulted in having 50% of the Duchenne protein omitted from the final protein, and yet he was still walking at 61 years old, very inconsistent, to say the least, of a Duchenne patient, who would be long expired long before 61 and in a wheelchair typically in their early teens. So we hope we have that opportunity to discuss that. On the precedent, I mean, there is one FDA. There are lots of divisions, but there's one FDA. And so one would assume that the precedent of other approvals is relevant. Every file stands on its own, and there are unique aspects of every file. But certainly, they are relevant to the discussion. There have been 4 instances in which the agency has had an opportunity to review data for therapies that induce shortened dystrophin as the 9001 dystrophin is shortened, often very shortened, sometimes as much as 40% reduced and are functional, and there are 4 approvals on that basis. So we would assume that, that is relevant. The difference -- the most significant big difference here between 9001 and those other approvals is that, while those other approvals were wonderful and have done an enormous amount of good for patients, the amount of dystrophin that's made by 9001 and the very powerful promoter used to make 9001 is far more than an order of magnitude more -- multiples more than an order of magnitude more than the dystrophin made by the precedent approval. So we do think there is some relevance to that, although of course, in addition to that, this file does stand on its own and has to be reviewed on its own.

[Operator Instructions] Our next question comes from the line of Gavin Clark-Gartner with Evercore ISI.

I'm just wondering if there's any discussion over the last few months or weeks on the correlation of microdystrophin expression levels to functional benefit, particularly in a Study 102 cohort that was underdosed?

I think one of the issues that we'll discuss at the Adcom is what is the association between dystrophin and it's effect on biomarkers, and it's functional effects. So I do think that will be something that will be -- we'll discuss at the Adcom. We think there's a very strong statistically significant positive association there in addition to the fact that we've seen a strong statistically significant between group differences across our various studies. So we look forward to having those discussions.

Our next question comes from the line of Tim Lugo with William Blair.

This is Lachlan on for Tim. Doug, I was just wondering, as we think about the translation of expression to clinical benefit, have you presented anything like a responder analysis? Or can you maybe speak to whether any patients that have received the intended dose of 9001 haven't displayed the clinical benefit?

We see a very strong association between the expression of 9001 and clinical benefit, and we've seen that in addition to seeing the study results versus natural history or where properly match the placebo arm. We look forward to showing all of that, discussing all that information at the advisory committee. You don't see a linear effect for the simple reason that we're getting such a robust expression that we're above a threshold amount for the vast majority of patients. You've seen there's a paper -- 2018 paper called the [indiscernible] paper that suggests that even 0.5% of dystrophin or less is associated with a phenotypic difference between those who have it and those who don't and that you get to as much as 5% dystrophin, you see a transformative benefit here. Of course, we're not getting 0.5% or 5%. We're seeing vastly more dystrophin than that. So we're kind of above that threshold amount for the vast majority of patients that didn't have the opportunity to get 9001.

Thank you. I would now like to hand the conference back over to Mr. Doug Ingram for closing remarks.

Well, thank you very much for joining us this evening. Obviously, I'll repeat what I said at the beginning. I am, of course, disappointed to have to tell you that there was a change in perspective on an Adcom. It was only a couple of weeks ago that we said there wasn't an Adcom, and now we're saying there is. But with that said, I want to be clear and really emphasize that, first of all, we're not substantively disappointed with an advisory committee. We think there is -- while it's work, there is an enormous opportunity and the ability in a public forum to really share all of the wealth of information that supports the benefits of 9001 to the patients who are receiving it. And I can assure you, we are going to be very well prepared to present well at that committee. We've already done an enormous amount of work. We're not at all caught off guard from a preparation perspective with respect to an advisory committee, and so we look forward to that opportunity to share that information publicly with you. And with that, have a wonderful evening and a good weekend.

This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone, have a wonderful day.